Quinacrine Inhibits Hepatocellular Carcinoma Growth and Enhances the Anti-HCC Effects of Lenvatinib

Hepatocellular Carcinoma (HCC) is a highly prevalent cancer worldwide, necessitating effective treatment options. However, current treatments do not provide satisfactory results. Quinacrine, a synthetic drug belonging to the 9-aminoacridine family, has demonstrated promising antitumor effects. The objective of the current study is to evaluate the anti-HCC effect of Quinacrine and explore whether quinacrine can improve the anti-HCC response of lenvatinib in vitro and in vivo. The HepG2 and MHCC-97H cells were treated with Quinacrine. Cell proliferation and cell apoptosis were assessed using the Cell Counting Kit-8 (CCK8) Assay, Colony Formation Assay, and Annexin V/7-AAD staining method. The invasion and migratory ability of HepG2 and MHCC-97H cells were assessed by Transwell Assay. The level of ROS of HCC cells was measured using a ROS-kit by Flow cytometric analysis. Besides, an in vivo study was performed in the Balb/c nude mice bearing MHCC-97H tumors to analyze the function of Quinacrine in tumor growth. Quinacrine can decrease cell viability in HepG2 and MHCC-97H cells, but not affect LO2 cells. Quinacrine impaired the colony formation, invasion and migratory ability in half-maximal inhibitory concentration (IC50). Quinacrine also significantly induced apoptosis in HepG2 and MHCC-97H cells in a concentrationdependent manner. On the one hand, ROS was significantly up-regulated in HCC cells after quinacrine treatment. On the other hand, We found quinacrine blocked autophagy flux in HepG2 and MHCC-97H cells. Moreover, Quinacrine significantly enhances the anti-HCC efficacy of lenvatinib in vitro. In the mouse MHCC-97H model, We found that combination therapy with Quinacrine and lenvatinib resulted in a smaller tumor volume and weight than inoculated with lenvatinib alone. Our findings demonstrated that quinacrine exerts anti-HCC effects and sensitizes hepatocellular carcinoma to lenvatinib. Collectively, our study provides novel therapeutic insights for managing HCC and offers a valuable strategy for future clinical interventions in this field.